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SARS-CoV-2 causes brain inflammation and induces Lewy body formation in macaques

Ingrid H.C.H.M. Philippens, View ORCID ProfileKinga P. Böszörményi, Jacqueline A. Wubben, Zahra C. Fagrouch, Nikki van Driel, Amber Q. Mayenburg, Diana Lozovagia, Eva Roos, Bernadette Schurink, Marianna Bugiani, Ronald E. Bontrop, Jinte Middeldorp, Willy M. Bogers, Lioe-Fee de Geus-Oei, Jan A.M. Langermans, Marieke A. Stammes, Babs E. Verstrepen, Ernst J. Verschoor
doi: https://doi.org/10.1101/2021.02.23.432474
Ingrid H.C.H.M. Philippens
1Biomedical Primate Research Centre (BPRC), Lange Kleiweg 161, 2288GJ Rijswijk, The Netherlands
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  • For correspondence: philippens@bprc.nl
Kinga P. Böszörményi
1Biomedical Primate Research Centre (BPRC), Lange Kleiweg 161, 2288GJ Rijswijk, The Netherlands
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  • ORCID record for Kinga P. Böszörményi
Jacqueline A. Wubben
1Biomedical Primate Research Centre (BPRC), Lange Kleiweg 161, 2288GJ Rijswijk, The Netherlands
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Zahra C. Fagrouch
1Biomedical Primate Research Centre (BPRC), Lange Kleiweg 161, 2288GJ Rijswijk, The Netherlands
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Nikki van Driel
1Biomedical Primate Research Centre (BPRC), Lange Kleiweg 161, 2288GJ Rijswijk, The Netherlands
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Amber Q. Mayenburg
1Biomedical Primate Research Centre (BPRC), Lange Kleiweg 161, 2288GJ Rijswijk, The Netherlands
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Diana Lozovagia
1Biomedical Primate Research Centre (BPRC), Lange Kleiweg 161, 2288GJ Rijswijk, The Netherlands
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Eva Roos
2Department of Pathology, Amsterdam UMC, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands
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Bernadette Schurink
2Department of Pathology, Amsterdam UMC, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands
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Marianna Bugiani
2Department of Pathology, Amsterdam UMC, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands
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Ronald E. Bontrop
1Biomedical Primate Research Centre (BPRC), Lange Kleiweg 161, 2288GJ Rijswijk, The Netherlands
3Department of Biology, Theoretical Biology and Bioinformatics, Utrecht University, Padualaan 8, Utrecht, The Netherlands
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Jinte Middeldorp
1Biomedical Primate Research Centre (BPRC), Lange Kleiweg 161, 2288GJ Rijswijk, The Netherlands
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Willy M. Bogers
1Biomedical Primate Research Centre (BPRC), Lange Kleiweg 161, 2288GJ Rijswijk, The Netherlands
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Lioe-Fee de Geus-Oei
5Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, The Netherlands
6Biomedical Photonic Imaging Group, University of Twente, Drienerlolaan 5, 7522ND Enschede, The Netherlands
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Jan A.M. Langermans
1Biomedical Primate Research Centre (BPRC), Lange Kleiweg 161, 2288GJ Rijswijk, The Netherlands
4Department Population Health Sciences, Division of Animals in Science and Society, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584CL Utrecht, The Netherlands
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Marieke A. Stammes
1Biomedical Primate Research Centre (BPRC), Lange Kleiweg 161, 2288GJ Rijswijk, The Netherlands
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Babs E. Verstrepen
1Biomedical Primate Research Centre (BPRC), Lange Kleiweg 161, 2288GJ Rijswijk, The Netherlands
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Ernst J. Verschoor
1Biomedical Primate Research Centre (BPRC), Lange Kleiweg 161, 2288GJ Rijswijk, The Netherlands
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Abstract

SARS-CoV-2 may cause acute respiratory disease, but the infection can also initiate neurological symptoms. Here we show that SARS-CoV-2 infection causes brain inflammation in the macaque model. An increased metabolic activity in the pituitary gland of two macaques was observed by longitudinal positron emission tomography-computed tomography (PET-CT). Post-mortem analysis demonstrated infiltration of T-cells and activated microglia in the brain, and viral RNA was detected in brain tissues from one animal. We observed Lewy bodies in brains of all rhesus macaques. These data emphasize the virus’ capability to induce neuropathology in this nonhuman primate model for SARS-CoV-2 infection. As in humans, Lewy body formation is an indication for the development of Parkinson’s disease, this data represents a warning for potential long-term neurological effects after SARS-CoV-2 infection.

Teaser SARS-CoV-2 causes brain inflammation and Lewy bodies, a hallmark for Parkinson, after an asymptomatic infection in macaques.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵‡ These authors jointly supervised this work

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted May 05, 2021.
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SARS-CoV-2 causes brain inflammation and induces Lewy body formation in macaques
Ingrid H.C.H.M. Philippens, Kinga P. Böszörményi, Jacqueline A. Wubben, Zahra C. Fagrouch, Nikki van Driel, Amber Q. Mayenburg, Diana Lozovagia, Eva Roos, Bernadette Schurink, Marianna Bugiani, Ronald E. Bontrop, Jinte Middeldorp, Willy M. Bogers, Lioe-Fee de Geus-Oei, Jan A.M. Langermans, Marieke A. Stammes, Babs E. Verstrepen, Ernst J. Verschoor
bioRxiv 2021.02.23.432474; doi: https://doi.org/10.1101/2021.02.23.432474
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SARS-CoV-2 causes brain inflammation and induces Lewy body formation in macaques
Ingrid H.C.H.M. Philippens, Kinga P. Böszörményi, Jacqueline A. Wubben, Zahra C. Fagrouch, Nikki van Driel, Amber Q. Mayenburg, Diana Lozovagia, Eva Roos, Bernadette Schurink, Marianna Bugiani, Ronald E. Bontrop, Jinte Middeldorp, Willy M. Bogers, Lioe-Fee de Geus-Oei, Jan A.M. Langermans, Marieke A. Stammes, Babs E. Verstrepen, Ernst J. Verschoor
bioRxiv 2021.02.23.432474; doi: https://doi.org/10.1101/2021.02.23.432474

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